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Biomedical subjects

M Asano

Publications and source records attributed to M Asano.

At least 145 records · Page 8Linked to original sources
PubMed1998

[Color Doppler signal enhancement with SH/TH-508 in pancreatic tumors].

In this report, we showed the efficacy of a new contrast agent (SH/TA-508, Schering AG, Germany) for color Doppler imaging of the pancreatic tumors. In pancreatic ductal cancer, no enhancement of the lesion was observed, but vascular invasion by cancer became to be easily evaluated. On the other hand, hypervascular tumors such as islet cell tumor and cystadenocarcinoma, were increased in color Doppler signals of vessels by SH/TA-508. We concluded that SH/TA-508 was useful for evaluating the vascular invasion by pancreatic cancer as well as vascularity of hypervascular mass and solid component of cystic neoplasma.

Adenoma, Islet Cell↗
PubMed1998

[Results of combination therapy of UFT-E with low-dose CDDP for patients with advanced recurrent breast cancer].

CDDP, as a modulator for 5-FU, has already been described as a very effective treatment for gastrointestinal tract cancer. We administered a dose of 400 mg of UFT-E orally every day, and 10 mg of CDDP by drip infusion twice weekly, for more than 10 weeks to 12 outpatients with metastatic local, pulmonary, hepatic, osteal or multiple-organ cancer which showed a poor response to the pretreatment, and assessed its efficacy and drug toxicity. In terms of the clinical efficacy of this therapy, CR was noted in one patient and PR in 2 patients with a response rate of 25%. The incidence of drug toxicity was low. Complications included temporal transient nausea and anorexia in two patients and leukopenia grade 2 as bone marrow suppression in 3 patients. From the standpoint of QOL, as well as in terms of both antitumor effect and drug toxicity, the therapy mentioned above was believed to be effective for outpatients with advanced recurrent breast cancer.

Administration, Oral↗
PubMed1998

[Prevention of contamination with a heat-and-moisture-exchanger (HME) and bacterial filter during clinical anesthesia].

Although the use of HME and bacterial filter is a common practice to protect the anesthesia machine as well as the patients from bacterial contaminants, there is no report demonstrating the effectiveness of this filter in clinical anesthesia setting. We evaluated the actual effectiveness of the filter during clinical use. While the anesthesia breathing circuit, two bacterial filters (BB 50 T, Nihon PALL) and anesthesia bag, which were sterilized with ethylen oxide gas (EOG), were connected to the anesthesia machine and used continuously for one week, EOG sterilized HME and bacterial filter (BB 25 A, Nihon PALL) were changed before each anesthesia. Culture samples were taken from the BB 25 A, the breathing circuit and the machine side of the BB 50 T. Of the 117 BB 25 A samples taken, 6 were positive for Micrococcus, alpha-Streptococcus, Bacillus, and Staphylococcus epidermidis. From 21 breathing circuit "internal" samples, one was positive for Bacillus, Staphylococcus epidermidis. But the contamination from outside sources was suspected, since all the BB 25 as used with this circuit were negative. Use of BB 25 A prevents contamination of the breathing circuit for a period of one week. If we use BB 25 A in every anesthesia case, the changing of the breathing circuit is unnecessary, reducing the cost and simplifying procedures during clinical practice.

Anesthesiology↗
PubMed1997

Pharmacological characterization of a novel, orally active, nonpeptide bradykinin B2 receptor antagonist, FR167344.

To investigate the pathophysiological role of bradykinin and to develop a drug for inflammatory diseases, we discovered an orally active, nonpeptide bradykinin B2 receptor antagonist, FR167344, N-[N-[3-[(3-bromo-2-methylimidazo[1,2-a]pyridin-8-yl)oxymethyl]-2, 4dichlorophenyl]-N-methylaminocarbonylmethyl]-4-(dimethyl aminocarbonyl) cinnamylamide hydrochloride. This compound competitively displaced [3H]bradykinin binding to bradykinin B2 receptors present in guinea-pig ileum membrane with an IC50 value of 6.6 X 10(-10) M. In isolated guinea-pig ileum preparations, it also antagonized bradykinin-induced contraction with a pA2 value of 9.3. In human lung fibroblast IMR-90 cells, FR167344 displaced [3H]bradykinin binding to human bradykinin B2 receptors with an IC50 value of 1.3 X 10(-8) M, but not [3H]des-Arg10-kallidin binding to human bradykinin B1 receptors. In vivo, oral administration of FR167344 inhibited bradykinin-induced bronchoconstriction in guinea pigs and the bradykinin-induced hypotensive response for 6 h in rats. These results show that FR167344 is a potent, selective, orally active and long acting bradykinin B2 receptor antagonist.

Animals↗
PubMed1997

Cloning and characterization of mammalian 8-hydroxyguanine-specific DNA glycosylase/apurinic, apyrimidinic lyase, a functional mutM homologue.

8-Hydroxyguanine (8-OH-G) is one of the major DNA oxidation products implicated in mutagenesis induced by oxygen radical-forming agents, including ionizing radiation. It is also believed to be involved in spontaneous mutation induced by metabolically produced oxygen radicals. A mammalian homologue of 8-OH-G glycosylase/apurinic, apyrimidinic lyase (mutM homologue, MMH) has been identified in the EST database (for expressed sequence tags) through a homology search with yeast OGG1 protein. The human MMH protein (hMMH), 34% identical to the yeast OGG1 protein, is a member of the DNA repair protein superfamily. The hMMH gene was composed of seven exons, with the alternate last exon, exon 8, producing three major alternative splicing isoforms, because splicing of the sixth intron was optional. The hMMH protein expressed in Escherichia coli revealed the glycosylase activity and apurinic, apyrimidinic lyase activity on duplex DNA containing 8-OH-G. The hMMH protein can rescue a spontaneous mutator strain of E. coli lacking mutM and mutY. By the introduction of recombinant hMMH, the rate of mutation, the formation of rifampicin-resistant revertants, was reduced by 4-7 fold. Genomic structure analysis showed that 3' exons of the hMMH gene are transcribed on the antisense strand of the calcium-dependent calmodulin kinase 1 gene.

Alternative Splicing↗
PubMed1997

Growth retardation and early death of beta-1,4-galactosyltransferase knockout mice with augmented proliferation and abnormal differentiation of epithelial cells.

Carbohydrate chains on a glycoprotein are important not only for protein conformation, transport and stability, but also for cell-cell and cell-matrix interactions. UDP-Gal:N-acetylglucosamine beta-1,4-galactosyltransferase (GalT) (EC 2.4.1.38) is the enzyme which transfers galactose (Gal) to the terminal N-acetylglucosamine (GlcNAc) of complex-type N-glycans in the Golgi apparatus. In addition, it has also been suggested that this enzyme is involved directly in cell-cell interactions during fertilization and early embryogenesis through a subpopulation of this enzyme distributed on the cell surface. In this study, GalT-deficient mice were produced by gene targeting in order to examine the pathological effects of the deficiency. GalT-deficient mice were born normally and were fertile, but they exhibited growth retardation and semi-lethality. Epithelial cell proliferation of the skin and small intestine was enhanced, and cell differentiation in intestinal villi was abnormal. These observations suggest that GalT plays critical roles in the regulation of proliferation and differentiation of epithelial cells after birth, although this enzyme is dispensable during embryonic development.

Animals↗
PubMed1997

Eicosapentaenoic acid enhances nitric oxide production by cultured human endothelial cells.

It is unclear whether the abnormal relaxation seen in diabetes is due to decreased levels of nitric oxide (NO) and how eicosapentaenoic acid (EPA, C20:5 omega 3) affects the endothelial production of NO. We investigated the effects of EPA ethyl ester (EPA-E) and elevated glucose on NO production by human endothelial cells (HUE). EPA-E (0.3 mM) significantly enhanced [NO2] production and the intracellular concentration of free Ca2+ within 3 min after EPA-E was added to the cultures. High levels of glucose (27.5 mM) significantly increased endothelial glucose, sorbitol and fructose, and inhibited [NO2-] production. However, EPA-E (0.3 mM) prevented the inhibition of [NO2-] production due to the activation of the Ca(2+)-calmodulin system of NO synthase. EPA-E decreased the glucose-mediated inhibition of NO production by HUE. These results suggest this agent might ameliorate endothelial dysfunction associated with diabetes.

Calcium↗
PubMed1997

Renal effect of YM435, a new dopamine D1 receptor agonist, in anesthetized dogs.

The renal effects of YM435 ((-)-(S)-4-(3,4-dihydroxyphenyl)-7,8-dihydroxy -1,2,3,4-tetrahydroisoquinoline hydrochloride hydrate), a dopamine D1 receptor agonist, were investigated in anesthetized dogs. Intravenous infusion of YM435 (0.1-3 micrograms/kg per min) increased renal blood flow and decreased mean blood pressure in a dose-dependent manner with little effect on heart rate. Glomerular filtration rate, urine flow and urinary sodium excretion were concomitantly increased. The renal effect of YM435 by intravenous infusion at 0.3 microgram/kg per min was completely blocked by treatment with the selective dopamine D1 receptor antagonist SCH 23390 (7-chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-(1H)-3-benzazep ine hydrochloride). Furthermore, intravenous infusion of YM435 (0.3 microgram/kg per min) reversed the angiotensin II-induced decreases in renal blood flow, glomerular filtration rate, urine flow and urinary sodium excretion, and prevented the decrease in renal blood flow, glomerular filtration rate and urine flow induced by renal nerve stimulation and platelet-activating factor (PAF). These results suggest that intravenous administration of YM435 produces renal vasodilating and diuretic/natriuretic effects by stimulation of dopamine D1 receptors, and demonstrate that YM435 can inhibit angiotensin II-, renal nerve stimulation- and PAF-induced renal dysfunction.

Anesthesia↗
PubMed1997

Extracellular Mg2+ inhibits receptor-mediated Ca(2+)-permeable non-selective cation currents in aortic smooth muscle cells.

The effects of extracellular Mg2+ on receptor-mediated Ca(2+)-permeable non-selective cation currents were investigated in a cultured aortic smooth muscle cell line (A7r5) from rat thoracic aorta, using the whole-cell voltage-clamp technique. Under the Cs(+)-containing internal solution, both vasopressin and endothelin-1 (100 nM) activated a long-lasting inward current with a high noise level. The reversal potential of these agonists-induced current was approximately +0 mV, and was not significantly altered by the replacement of [Cl-]i or [Cl-]o, suggesting that the inward current was a cation-selective channel. La3+ and Cd2+ (1 mM) almost completely abolished the vasopressin or endothelin-induced non-selective cation current; however, nifedipine (10 microM) failed to inhibit it significantly. Extracellular Mg2+ (3-20 mM) also markedly inhibited the vasopressin- or endothelin-induced non-selective cation current in a concentration-dependent manner. When a non-hydrolysable GTP-analogue, GTP gamma S (1 mM), was applied from the patch pipette, the non-selective cation current was gradually activated even in the absence of agonist (vasopressin or endothelin-1), probably due to the direct activation of GTP-binding proteins coupled to the receptors. Extracellular Mg2+ (3-20 mM) also suppressed the activation of non-selective cation current induced by GTP gamma S, suggesting that the inhibitory sites of Mg2+ are not located on the receptors. These results suggest that extracellular Mg2+ inhibits receptor-mediated non-selective cation current, which may contribute to the relaxation effects of Mg2+ in vascular smooth muscle cells.

Animals↗
PubMed1997

Macrophage antigen-1 positive cells are essential in the defense against Theiler's virus strain GD VII infection in the spinal cord.

Acute encephalomyelitis caused by Theiler's virus strain GD VII resembles human poliomyelitis, and T cells are essential in eliminating the virus from the brain, though not from the spinal cord. We speculated that macrophage-lineage cells might play a crucial role in eliminating the virus from the spinal cord. To analyse the role of macrophage-lineage cells in the infection, antibodies specific for beta2 integrin, as well as an anti-leukocyte function antigen 1 (LFA-1) monoclonal antibody (MAb) and an anti-complement receptor type 3 (CR3) MAb were used to deplete the corresponding cell populations in Theiler's virus-infected mice. Infiltration of CD8+ T cells into the brain and spinal cord was inhibited by the administration of the anti-LFA-1 MAb, and viral replication was augmented only in the brain. The number of CD4+ T cells and macrophage antigen-1 (Mac-1[+]) cells in the brain and spinal cord were not decreased by anti-LFA-1 MAb treatment. Anti-CR3 MAb treatment led to decrease of Mac-1(+) cells in the brain and spinal cord. The viral replication in the spinal cord of anti-CR3 MAb treated mice was augmented, but not that in the brain. These results indicate that the defense mechanism against Theiler's virus strain GD VII is dependent on Mac-1(+) cells in the spinal cord.

Animals↗
PubMed1997

Effect of YM934, a KATP channel opener, on airway hyperresponsiveness induced by platelet activating factor in guinea-pigs.

The effect of YM934 (2-(3,4-dihydro-2,2-dimethyl-6-nitro-2H-1, 4-benzoxazin-4-yl)pyridine N-oxide) on airway hyperresponsiveness induced by platelet activating factor (PAF) was investigated in anesthetized guinea-pigs. Bronchoconstrictor responses to histamine were enhanced by intravenous (i.v.) infusion of PAF (600 ng/kg/h for 1 h). The KATP channel opener, YM934 (10-100 micrograms/ kg), given by i.v. bolus injection or i.v. infusion (75 min) dose-dependently inhibited this PAF-induced airway hyperresponsiveness. In the normal control group, i.v. bolus injection of YM934 dose-dependently reduced the bronchoconstrictor responses to histamine. However, i.v. infusion of YM934 (100 micrograms/kg) had almost no effect on responsiveness. Pretreatment with capsaicin (50 micrograms/kg, s.c.), a depleter of neuropeptides, partially prevented the development of PAF-induced airway hyperresponsiveness. In contrast, phosphoramidon (2.5 mg/kg, i.v.), an inhibitor of neutral endopeptidase, enhanced the airway hyperresponsiveness induced by PAF. Furthermore, YM934 inhibited PAF-induced airway hyperresponsiveness in guinea-pigs pretreated with capsaicin or phosphoramidon. The present results suggest that YM934 given by i.v. infusion reduces PAF-induced airway hyperresponsiveness at doses insufficient to produce a bronchodilatory effect. Further, the mechanism of YM934's inhibitory effect on airway hyperresponsiveness may involve bronchodilatory and other unidentified effects, such as a decrease in the release of neuropeptides from sensory nerve terminals.

Airway Resistance↗
PubMed1997

Epicoprostanol found in adipocere from five human autopsies.

Adipocere formation is well known as a later postmortem change. We collected adipocere from five male victims which had been submerged under the sea or fresh water for 1 mon to 4 yr. Fresh subcutaneous fat of a male victim who died from a cerebral contusion was used as the control. The samples were homogenized, and the lipids were extracted with chloroform and methanol followed by injection into a gas chromatograph and a gas chromatograph-mass spectrometer. We detected hydroxy fatty acids (10-hydroxyoctadecanoic acid and 10-hydroxyhexadecanoic acid) as well as 10-ketooctadecanoic acid in adipocere, but not in the control. In addition, we found for the first time a cholesterol-related peak with a molecular ion of 388 in adipocere and identified it as epicoprostanol, suggesting not only oxidation but also reduction had occurred during the formation of adipocere. In addition, we showed the time-course of epicoprostanol accumulation. The relationship between the time of adipocere formation and the characteristic lipid composition is discussed.

Adipose Tissue↗
PubMed1997

Pulmonary blood flow regulates plasma tissue plasminogen activator concentrations in patients with congenital heart defects.

OBJECTIVE: The wall shear stress generated by blood flow regulates the expression of fibrinolytic proteins by endothelial cells in vitro. In the present study, the effects of pulmonary blood flow on fibrinolytic activity were studied in patients with congenital heart defects and pulmonary hypertension. METHODS: Twenty-seven patients who underwent cardiac operation because of congenital heart defects were divided into four groups according to the severity of pulmonary hypertension. Group I consisted of seven patients with normal pulmonary artery pressure, group II consisted of nine patients with pulmonary hypertension caused by increased pulmonary blood flow, group III consisted of six patients with pulmonary hypertension caused by increased pulmonary vascular resistance, and group IV consisted of five patients with tetralogy of Fallot. Plasma concentrations of tissue plasminogen activator, plasmin, and thrombin were assayed as the inhibitor-bound forms. RESULTS: The preoperative concentration of tissue plasminogen activator was higher in group II than in all other groups (p = 0.0003). However, the postoperative concentration decreased only in patients in group II when compared with the preoperative value (p = 0.01). By Pearson's correlation analysis, pulmonary blood flow was found to correlate with the preoperative concentration of tissue plasminogen activator (95% confidence interval = 3.99 to 10.58, p = 0.0001). No definite conclusion was found for the relationship between tissue plasminogen activator and plasmin concentration. Further, the preoperative thrombin concentration was similar in all groups. CONCLUSIONS: These findings suggest that pulmonary blood flow may regulate the plasma concentration of tissue plasminogen activator in patients with congenital heart defects.

Child, Preschool↗
PubMed1997

Restoration of nitric oxide production by aldose reductase inhibitor in human endothelial cells cultured in high-glucose medium.

The effects of elevated glucose and aldose reductase inhibitor (ARI:ONO-2235) on nitric oxide (NO) production in cultured human umbilical endothelial cells (HUVEC) were evaluated. Aldose reductase and nitric oxide synthase(NOS) share NADPH as an obligate cofactor, therefore it is suggested that the enhanced of glucose flux (27.5 mM) by aldose reductase inhibited NO production by blunting NOS activity. However, the addition of ONO-2235 (100 microM) prevented the inhibition of [NO2-] production. Since ARI decreases glucose-mediated inhibition of NO production in HUVEC. this agent might ameliorate endothelial function associated with diabetes.

Aldehyde Reductase↗
PubMed1997

Omega-3 polyunsaturated fatty acids inhibit migration of human vascular smooth muscle cells in vitro.

Arterial smooth muscle cell migration from the media to the intima is a crucial process in the pathogenesis of atherosclerosis. Platelet-derived growth factor (PDGF) has been proposed to play a key role in the development of advanced atherosclerotic lesions by stimulating the migration and proliferation of vascular smooth muscle cells. Polyunsaturated fatty acids (PUFA) of the omega-3 series, extracted from fish oil has been shown to have beneficial effects on atherosclerosis. In this study, we evaluated the effects of omega-3 PUFA on the migration of human aortic smooth muscle cell (hASMC) in vitro. The migration assay was performed according to the Capsoni's method using transwell culture plates. PDGF, fibrinogen or 10% FCS significantly stimulated hASMC migration, however, omega-3 PUFA significantly inhibited PDGF-induced migration of hASMC. These results suggest that the inhibitory effect of omega-3 PUFA on cell migration may be an important aspect by which omega-3 PUFA exerts its antiatherosclerotic influence.

Cell Movement↗
PubMed1997

Acute effects of thromboxane dual blocker (KDI-792) on different portions of lower limb blood flow--a study using Doppler ultrasonography and laser Doppler flowmetry in type 2 diabetic patients.

The acute effects of a newly synthesized thromboxane dual blocker (KDI-792), a combined thromboxane synthase inhibitor and receptor antagonist, on lower limb circulation were examined using two-dimensional color and pulse Doppler ultrasonography and laser Doppler flowmetry. A randomized single-masked, placebo-controlled trial was performed on 36 type 2 diabetic patients with minimally impaired baseline flow. The anatomical cross-sectional area (CSA), maximum flow velocity (MFV) and flow volume index (FVI) in the right dorsal pedis artery (DPA) and right femoral artery (FA) were determined by Doppler ultrasonography before and 45 and 90 minutes after the administration of either 100 or 200 mg of KDI-792 to the dose groups or placebo to the control group. Periflux blood flow (PBF) in the right foot was determined simultaneously by laser Doppler flowmetry. Both CSA and MFV in the dose groups were significantly increased in both the FA and DPA. FVI was markedly increased from 21.4 +/- 3.7 to 68.3 +/- 26.8 in the DPA (M +/- SD, P < 0.01) and from 365.4 +/- 35.3 to 771.7 +/- 75.7 in the FA (P < 0.01) in the 200 mg dose group. In the 100 mg dose group, FVI was markedly increased from 20.0 +/- 8.7 to 68.3 +/- 26.8 (P < 0.01) in the DPA and from 372.5 +/- 130.0 to 677.5 +/- 187.8 (P < 0.01) in the FA. PBF was also increased in both dose groups (from 4.15 +/- 1.4 to 7.0 +/- 4.0 ml/min/100 g tissue in the 200 mg dose group, P < 0.01), whereas there were no significant changes in either measurement in the control group. There were no significant changes in pulse rate or blood pressure after administration in either the dosage group or the placebo group. These and previous findings indicate that a single administration of KDI-792 markedly increases lower limb blood flow and might have a more potent vasodilating effect than that of prostaglandin I2 derivatives.

Aged↗
PubMed1997

Antianginal effects of YM430, a novel calcium entry-blocking and beta-adrenoceptor-blocking agent in several experimental angina models.

1. We evaluated the antianginal effects of YM430 in several experimental models in vitro and in vivo. 2. In isolated dog coronary artery, YM430 (10(-8)-10(-6) M) inhibited 3,4-diaminopyridine-induced rhythmic contractions with an IC50 value of 59.2 nM. 3. In anesthetized rats, YM430 (10-100 mg/kg PO) inhibited arginine vasopressin-induced ST-segment depression with an IC50 value of 36.6 mg/kg PO. 4. In anesthetized dogs, YM430 (0.3 mg/kg IV) significantly inhibited ST-segment elevation induced by coronary artery occlusion. 5. These findings suggest that YM430 may be of value in the treatment of various types of angina pectoris such as variant and stable angina.

4-Aminopyridine↗